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Exercise training and calpain inhibition prevent the IR‐induced degradation of myocardial calcium handling proteins and contractile dysfunction
Author(s) -
French Joel P,
Quindry John C,
Powers Scott K
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.lb13-c
Subject(s) - calpain , endoplasmic reticulum , cytosol , calcium , chemistry , reactive oxygen species , protein degradation , medicine , microbiology and biotechnology , endocrinology , biochemistry , biology , enzyme
Increases in reactive oxygen species (ROS), cytosolic Ca 2+ and activity of the calcium‐activated protease calpain contribute to ischemia‐reperfusion (IR) injury. Additionally, there is evidence to suggest that ROS may contribute to Ca 2+ overload and calpain activation by damaging critical Ca 2+ handling proteins. We have previously shown that exercise protects against IR‐induced oxidative stress and calpain activation; however, the mechanisms of this protection are unknown. Therefore, we tested the hypothesis that exercise training attenuates IR‐induced calpain activation through the preservation of critical Ca 2+ handling proteins. In sedentary animals, IR ( in vitro ) resulted in a decrease in both sarcoplasmic/endoplasmic reticulum Ca 2+ ATPase (SERCA2a) and L‐type Ca 2+ channel (LTCC) protein, as well as impaired myocardial function (systolic pressure, +dp/dt and –dp/dt). Both exercise and calpain inhibition attenuated IR‐induced calpain activation, the degradation of SERCA2a and LTCC and maintained myocardial function following IR. In addition, exercise training was associated with an increase in basal levels of LTCC protein in the heart. These findings suggest that exercise may regulate calpain activation, in part, through the maintenance of Ca 2+ handling proteins. Further, these data support the notion that calpain may regulate itself in a feed‐forward mechanism, cleaving Ca 2+ handling proteins, exacerbating IR‐induced Ca 2+ overload, leading to further calpain activation and myocardial injury. Supported by NIH HL072789 (SKP), AHA 0415135B (JPF).